Accuracy of tablet splitting for paediatric dosing: mass and content uniformity

To evaluate the accuracy of tablet splitting for paediatric dosing by assessing mass and content uniformity.

Whole, half, and quarter tablets of mercaptopurine, azathioprine, and spironolactone were prepared using a manual tablet splitter. Fragment mass and quarter-tablet drug content were assessed against European Pharmacopoeia criteria.

Split fragments showed high variability (coefficient of variation 8.6%-23.3%). Most failed European Pharmacopoeia mass uniformity criteria. Content analysis revealed only 50%-70% of quarters complied with acceptance limits, with ranges of 52%-133% of claim.

Tablet splitting introduces substantial dose variability undetectable by weighing alone. Where possible, low-strength tablets or alternative formulations should be preferred.